Incidence Of Clostridium Difficile-associated Diarrhea Research Articles

Incidence of diarrhea by Clostridium difficile in hematologic patients and hematopoietic stem cell transplantation patients: risk factors for severe forms and death.

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.

Probiotics reduce symptoms of antibiotic use in a hospital setting: A randomized dose response study

Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU® Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU® Restore probiotic 1.70×1010 CFU (high-dose, n=168), HOWARU® Restore probiotic 4.17×109 CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.

Procalcitonin as Adjunct Biomarker for Severe Clostridium difficile-associated Diarrhea

Purpose: Procalcitonin (PCT) has recently emerged as a useful adjunct in severe bacterial infections. Interferon (INF) -γ released in response to viral infections attenuates up-regulation of PCT, making it more specific for bacterial infections. The utility of PCT has been evaluated in various infections, such as pneumonia (community-acquired and ventilator-associated), severe sepsis and shock, urinary tract infection and febrile neutropenia. Few studies have investigated the use of PCT in acute intra-abdominal processes such as perforation, ischemia, acute appendicitis and pancreatitis. However, there has been no study to date evaluating the use of PCT in Clostridium difficile-associated diarrhea (CDAD). The incidence of CDAD (hospital- and community-acquired) continues to rise. Its severity is assessed by WBC count ≥15,000 or a serum creatinine level ≥1.5 times the baseline level. The aim of this study was to evaluate levels of PCT in patients with CDAD versus those with diarrhea of other etiologies, and assess the correlation between elevated PCT levels and severity of CDAD. Methods: This study was conducted at a tertiary care center over a period of 16 months (February 2011 - July 2012). Data were collected from all patients with diarrhea irrespective of the admitting diagnosis. Patients with bacteremia, UTI, pneumonia or neutropenia were excluded. All these patients had serum PCT drawn on admission along with stool studies for Clostridium difficile antigen; if the latter was positive, confirmation was obtained using Clostridium difficile toxin assay by polymerase chain reaction. A total of 157 patients with CDAD and 512 with non-CDAD were included. WBC count and serum creatinine levels were obtained in all these patients (age 20-98 years). Medians and Interquartile ranges (IQR) were compared using Mann-Whitney test. Cutoffs, sensitivity and specificity were obtained from receiver operator characteristic (ROC) curve. The associations were determined by a linear regression. Results: Patients with CDAD have much higher levels of PCT than patients with diarrhea of other etiologies. A PCT cutoff of 0.5ng/ml provided sensitivity of 90% and a specificity of 98%. Elevated WBC (≥15,000) and rise in creatinine ≥1.5 times baseline value were associated with higher PCT levels in patients with CDAD; for elevated WBC levels are r2=0.04, p=0.013 and for rise in creatinine r2=0.13, p<0.0001. The median for patients were 3.4 ng/L (IQR 1.5 to 12.8) while the median for controls were 0.27 ng/mL (IQR 0.14 to 0.41). Conclusion: Procalcitonin may be a valuable adjunct biomarker in distinguishing diarrhea from CDAD.

Treatment of an Initial Infection with Clostridium difficile in Patients with Inflammatory Bowel Disease

: Although the incidence of Clostridium difficile-associated diarrhea in the general population has increased dramatically over the past decade, an even greater rate of infection exists in patients with inflammatory bowel disease. Susceptibility in this population is likely inherent to the pathophysiology and treatment of these diseases. C. difficile infection can cause serious complications and death. Consequently, early diagnosis and initiation of effective antibacterial therapy is imperative. This article evaluates treatment recommendations for an initial episode of C. difficile infection in patients with inflammatory bowel disease based on the current guidelines and a Cochrane systematic review.

Risk factors for recurrence of clostridium difficile-associated diarrhoea.

Clostridium difficile associated disease (CDAD) is one of the most common causes of hospital-acquired diarrhea. Despite increasing incidence of clostridium difficile-associated diarrhea, there are few data on risk factors associated with its relapse. We studied retrospectively possible risk factors for the recurrence of CDAD; 124 patients fulfilled the criteria of CDAD during the study period between January 2006 and July 2009. After successful treatment, recurrence occurred in 20 patients. Nineteen patients (95%, p = 0.029) in the relapse group were on long term proton pump inhibitor therapy compared to 77 patients (74%) in the non-relapse group. There was no statistically significant difference in severity (CRP: p = 0.442, leucocytosis: p = 0.415) and length of hospitalization (p= 0.539) in both studied groups; however, CDAD-relapse was associated with more hospital readmissions and increased health care costs. Proton pump inhibitor therapy may be associated with increased risk of recurrence of CDAD, and represents a relevant, yet correctable risk factor. In patients at risk for CDAD, proton pump inhibitors should be used carefully.

Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children

Antibiotics are widely prescribed; however they can cause disturbances in gastrointestinal flora which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live organisms thought to balance the gastrointestinal flora. The primary objectives were to assess the efficacy and safety of probiotics for preventing Clostridium difficile-associated diarrhea (CDAD) or C. difficile infection in adults and children. On February 21, 2013 we searched PubMed (1966-2013), EMBASE (1966-2013), Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1), CINAHL (1982-2013), AMED (1985-2013), and ISI Web of Science. Additionally, we conducted an extensive grey literature search including contact with industry representatives. Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. Two authors independently and in duplicate extracted data and assessed risk of bias using pre-constructed, and piloted, data extraction forms. Any disagreements were resolved by a third adjudicator.For articles published in abstract form only, further information was sought by contacting principal authors. The primary outcome was the incidence of CDAD. Secondary outcomes included the incidence of C. difficile infection, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval (95% CI). Continuous outcomes (e.g. length of hospital) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias.The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. A total of 1871 studies were identified with 31 (4492 participants) meeting eligibility requirements for our review. Overall 11 studies were rated as a high risk of bias due mostly to missing outcome data. A complete case analysis (i.e. participants who completed the study) of those trials investigating CDAD (23 trials, 4213 participants) suggests that probiotics significantly reduce this risk by 64%. The incidence of CDAD was 2.0% in the probiotic group compared to 5.5% in the placebo or no treatment control group (RR 0.36; 95% CI 0.26 to 0.51). Sixteen of 23 trials had missing CDAD data ranging from 5% to 45%. These results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and were similar whether considering trials in adults versus children, lower versus higher doses, different probiotic species, or higher versus lower risk of bias. Our judgment is that the overall evidence warrants moderate confidence in this large relative risk reduction. We downgraded the overall quality of evidence for CDAD to 'moderate' due to imprecision. There were few events (154) and the calculated optimal information size (n = 8218) was more than the total sample size. With respect to the incidence of C. difficile infection, a secondary outcome, pooled complete case results from 13 trials (961 participants) did not show a statistically significant reduction. The incidence of C. difficile infection was 12.6% in the probiotics group compared to 12.7% in the placebo or no treatment control group (RR 0.89; 95% CI 0.64 to 1.24). Adverse events were assessed in 26 studies (3964 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 20% (RR 0.80; 95% CI 0.68 to 0.95). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. For the short-term use of probiotics in patients that are not immunocompromised or severely debilitated, we consider the strength of this evidence to be moderate. Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.

Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind, randomized, placebo-controlled clinical trial

Antibiotic-associated diarrhoea (AAD) is a frequent complication of systemic antibiotic therapy and Clostridium difficile-associated diarrhoea (CDAD) is its most serious form due to associated morbidity and mortality. This trial aimed to investigate whether the probiotic VSL#3 prevents AAD and CDAD in average-risk hospital patients. Adult hospital inpatients exposed to systemic antibiotics were recruited to this multicentre, randomized, double-blind, placebo-controlled trial. One sachet of VSL#3 or placebo was given twice daily for the length of the antibiotics course and for seven days thereafter. Primary outcomes were AAD and CDAD. Patients randomized to active (N = 117) and placebo (N = 112) groups were well-matched for baseline demographic patient data. No cases of CDAD were detected. The rate of AAD was significantly lower in the active group on per protocol analysis (0% active vs 11.4% placebo; P = 0.006). On intention-to-treat analysis the difference in AAD incidence (4.3% active vs 8.9% placebo; P = 0.19) was not significant. VSL#3 is associated with a significant reduction in the incidence of AAD in average-risk hospital inpatients exposed to systemic antibiotics. As the incidence of CDAD has fallen sharply, no cases of CDAD were found. Probiotic administration as prophylaxis for CDAD may not be indicated in average-risk hospital patients.

Does improving surface cleaning and disinfection reduce health care-associated infections?

Contaminated environmental surfaces provide an important potential source for transmission of health care-associated pathogens. In recent years, a variety of interventions have been shown to be effective in improving cleaning and disinfection of surfaces. This review examines the evidence that improving environmental disinfection can reduce health care-associated infections.

Coste de la diarrea asociada a Clostridium difficile en España

There are not available adequate studies of the costs of Clostridium difficile-associated diarrhea (CDAD) in Spain. The aim of the study is to estimate the cost of CDAD for the National Health Service (NHS). an economic model was carried out to calculate the cost per episode of CDAD (due to antimicrobials, prolonged hospitalization, surgical procedures, measures to control the infection, recurrences of infections treated) and the CDAD annual cost. Resources use in clinical practice was obtained through a Delphi panel of Spanish clinicians with expertise in CDAD and unit costs (€ 2012) from Spanish Sources. An estimated 7,601 episodes of CDAD occur annually in Spain (incidence of 17.1 episodes/year/10,000 hospital discharges) with an annual cost to the NHS of € 32,157,093. Cost per episode of CDAD: € 3,901 (initial infection), € 4,875 (first recurrence) and € 5,916 (second recurrence). Total cost of recurrences: € 10,426,750 annually. The 95.6% of spending is due to the prolonged hospitalization, 0.5% to antibiotic treatment, 2.8% for surgery and 1.1% for measures of control infection. Study results are sensitive to incidence and case fatality rate of CDAD in Spain and the prolongation of duration of hospital stay due to CDAD. According to this study, the expense associated with CDAD is primarily due to the prolongation of hospitalization and has a great economic impact on the NHS.

Incidence of &amp;lt;i&amp;gt;Clostridium difficile&amp;lt;/i&amp;gt;-associated diarrhea in patients using proton pump inhibitors: A Japanese study

Objective: The incidence of Clostridium difficile-associated diarrhea (CDAD) has increased in many developed countries. In addition to previous use of antimicrobials, use of proton pump inhibitors (PPIs) is thought to increase the incidence of CDAD. However, most previous studies that showed a positive relationship between PPI use and CDAD were conducted retrospectively in Western countries. We investigated whether the use of PPIs increases the incidence of CDAD in Japan. Methods: The study was carried out with all the patients admitted to the department of internal medicine of Teikyo University Hospital from April 2009 to June 2009. Clinical data were obtained from medical records. CDAD was defined as detection of CD toxin from stool samples in diarrheal patients. PPI users were defined as patients that were prescribed with PPI for more than 30 days at the detection of CD toxin. The results of Clostridium difficile (CD) toxin were collected until April 2011. Results: A total of 793 patients were included, and PPIs were prescribed to 489 patients (59.8%). The average age of PPI users was higher than that of PPI nonusers (68.9 vs. 63.1 years). Among the 489 PPI users, 19 patients developed CDAD, while 4 developed CDAD among the 304 PPI nonusers. The relative risk of PPI use on the incidence of CDAD was 3.20 in univariate analysis (95% confidence interval, 1.10 to 9.32, p = 0.04), although the hazard ratio in multivariate analysis was 1.23 (95% confidence interval, 0.35 to 3.83, p = 0.82). Conclusions: There was no association between CDAD occurrence and PPI use in patients in Japan.

Probiotics for the Prevention ofClostridium difficile–Associated Diarrhea

Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile–associated diarrhea (CDAD). To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources. Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD. Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome. Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%). In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events. None.

Progress of laboratory diagnostic methods ofClostridium difficile infection

Clostridium difficile is a gram-positive, anaerobic spore-forming bacillus commonly found in the environment and human gut.Excessive use of antibiotics，immunosuppressive agents and chemotherapy drugs may lead to overgrowth of the toxic strain of Clostridium difficile with high resistance，which are supposed to be the major contributing factors leading to Clostridium difficile associated diarrhea(CDAD).The globally increasing incidence of CDAD，especially the outbreak of nosocomial infection caused by the hypervirulent strain in North America，arouse worldwide attention. For providing new ideas to the early diagnosis and treatment of CDAD，this review summarize the latest development on pathogenesis and rapid laboratory diagnosis of Clostridium difficile.（Chin J Lab Med,2012,35:692-696） Key words: Clostridium difficile; Enterocolitis，pseudomembranous; Laboratory techniques and procedures

Clostridium difficile -Associated Diarrhea and Proton Pump Inhibitor Therapy: A Meta-Analysis

Clostridium difficile-associated diarrhea (CDAD) is a major cause of morbidity and increasing health-care costs among hospitalized patients. Although exposure to antibiotics remains the most documented risk factor for CDAD, attention has recently been directed toward a plausible link with proton pump inhibitors (PPIs). However, the results of studies on the association between CDAD and PPIs remain controversial. We have conducted a meta-analysis to summarize the association between PPIs and CDAD among hospitalized patients. A systematic search of published literature on studies that investigated the association between PPIs and CDAD from 1990 to 2010 was conducted on Medline and PubMed. The identified articles were reviewed for additional references. The most adjusted risk estimates were extracted by two authors and summarized using random effects meta-analysis. We also conducted a subgroup analysis by study design. Publication bias was evaluated using the Begg and Egger tests. A sensitivity analysis using the Duval and Tweedie "trim-and-fill" method has also been performed. Twenty-three studies including close to 300,000 patients met the inclusion criteria. There was a 65% (summary risk estimate 1.69 with a 95% confidence interval (CI) from 1.395 to 1.974; P<0.000) increase in the incidence of CDAD among patients on PPIs. By study design, whether case-control study (17) or cohort study (6), there was still a significant increase in the incidence of CDAD among PPI users. The risk estimates were 2.31 (95% CI from 1.72 to 3.10; P<0.001) and 1.48 (95% CI from 1.25 to 1.75; P<0.001) for cohort and case-control studies, respectively. There is sufficient evidence to suggest that PPIs increase the incidence of CDAD. Our meta-analysis shows a 65% increase in the incidence of CDAD among PPI users. We recommend that the routine use of PPIs for gastric ulcer prophylaxis should be more prudent. Establishing a guideline for the use of PPI may help in the future with the judicious use of PPIs. Further studies, preferably prospective, are needed to fully explore the association between PPIs and CDAD.

Clostridium difficile–Associated Diarrhea at a Community Hospital: Ten-Year Analysis of Infection Rates and the Relationship with Proton Pump Inhibitor Use

Purpose To investigate the relationship between proton pump inhibitor (PPI) use and the incidence of Clostridium difficile–associated diarrhea (CDAD) at a community hospital. Methods The number of inpatient admissions, inpatient cases of CDAD, and PPI and antimicrobial doses were collected for each year from 2000 to 2009. Correlations between incidence of CDAD and doses of PPI and antimicrobials were calculated using Spearman's rank correlation coefficient analysis. Results The incidence of CDAD correlated with the number of doses of PPI per admission (ρ = 0.891, P &lt; .001) and with the number of doses of antimicrobials per admission (ρ = 0.806, .005 &gt; P &gt; .001). The correlation of CDAD incidence with high-risk and low-risk antimicrobials was significant for both groups (ρ = 0.624, .05 &gt; P &gt; .025, and ρ = 0.881, P &lt; .001, respectively). The correlation of oral and intravenous PPI dosing and CDAD incidence was significant for both (ρ=0.903, P &lt; .001, and ρ=0.806, .005 &gt; P &gt; .001, respectively). Multiple regression analysis with both antimicrobials and PPIs as predictors of CDAD was statistically significant ( R2 = 0.75, P = .0082). Conclusion The incidence of CDAD is correlated with PPI use. Antimicrobials are a well-established risk factor for CDAD, and our study reinforces this. Prescribers should consider limiting risk of CDAD by the judicious use of PPIs.

Risk Factors for Recurrence of Clostridium Difficile-associated Diarrhea

Background: Clostridium difficile associated disease (CDAD) is one of the most common causes of hospital-acquired diarrhea. Despite increasing incidence of clostridium difficile-associated diarrhea, there are few data on risk factors associated with its relapse.

Inappropriate Use of Gastric Acid Suppression Therapy in Hospitalized Patients with Clostridium difficile—Associated Diarrhea: A Ten-Year Retrospective Analysis

Purpose. The incidence of Clostridium difficile-associated diarrhea (CDAD) has steadily increased over the past decade. A multitude of factors for this rise in incidence of CDAD have been postulated, including the increased use of gastric acid suppression therapy (GAST). Despite the presence of practice guidelines for use of GAST, studies have demonstrated widespread inappropriate use of GAST in hospitalized patients. We performed a retrospective analysis of inpatients with CDAD, with special emphasis placed on determining the appropriateness of GAST. Methods. A retrospective analysis was conducted at a multidisciplinary teaching hospital on inpatients with CDAD over a 10-year period. We assessed the use of GAST in the cases of CDAD. Data collection focused on the appropriate administration of GAST as defined by standard practice guidelines. Results. An inappropriate indication for GAST was not apparent in a majority (69.4%) of patients with CDAD. The inappropriate use of GAST was more prevalent in medical (86.1%) than on surgical services (13.9%) (P < 0.001). There were more cases (67.6%) of inappropriate use of GAST in noncritical care than in critical care areas (37.4%) (P < 0.001). Conclusion. Our study found that an inappropriate use of inpatient GAST in patients with CDAD was nearly 70 percent. Reduction of inappropriate use of GAST may be an additional approach to reduce the risk of CDAD and significantly decrease patient morbidity and healthcare costs.

Clostridium Difficile Colitis

Clostridium difficile-associated diarrhea (CDAD) is an increasingly important diagnosis in solid organ transplant recipients, with rising incidence and mortality. We describe the incidence, risk factors, and outcomes of colectomy for CDAD after solid organ transplantation. Patients with CDAD were identified from a prospective transplant database. Complicated Clostridium difficile colitis (CCDC) was defined as CDAD associated with graft loss, total colectomy, or death. From 1999 to 2010, we performed solid organ transplants for 1331 recipients at our institution. The incidence of CDAD was 12.4% (165 patients); it increased from 4.5% (1999) to 21.1% (2005) and finally 9.5% (2010). The peak frequency of CDAD was between 6 and 10 days posttransplantation. Age more than 55 years (hazard ratio [HR]: 1.47, 95% confidence interval [CI]=1.16-1.81), induction with antithymocyte globulin (HR: 1.43, 95% CI=1.075-1.94), and transplant other than kidney alone (liver, heart, pancreas, or combined kidney organ) (HR: 1.41, 95% CI=1.05-1.92) were significant independent risk factors for CDAD. CCDC occurred in 15.8% of CDAD cases. Independent predictors of CCDC were white blood cell count more than 25,000/μL (HR: 1.08, 95% CI=1.025-1.15) and evidence of pancolitis on computed tomography scan (HR: 2.52, 95% CI=1.195-5.35). Six patients with CCDC underwent colectomy with 83% patient survival and 20% graft loss. Of the medically treated patients with CCDC (n=20), the patient survival was 35% with 100% graft loss. We have identified significant risk factors for CDAD and predictors of progression to CCDC. Furthermore, we found that colectomy can be performed with excellent survival in selected patients.

Changing incidence and clinical manifestations of Clostridium difficile-associated diarrhea detected by combination of glutamate dehydrogenase and toxin assay in Northern Taiwan

The incidence of Clostridium difficile-associated diarrhea (CDAD) is increasing worldwide. Spread of an epidemic hypervirulent strain in southern Taiwan was associated with poor outcome. This prospective study evaluates the incidence and clinical manifestation of CDAD following a hospital-wide hand hygiene promotion program in a 2,200-bed teaching hospital in northern Taiwan. From June 1, 2010 to October 31, 2010, a predefined protocol was used to actively survey CDAD at 11 high-risk units. Stool samples of patients with antibiotic-associated diarrhea (AAD) were submitted for stool culture and toxin A/B assay using a combined enzyme immunoassay. CDAD was diagnosed by a positive toxin assay. The incidence of CDAD was 0.45/1000 patient-days and was highest in medical intensive care units (7.9/1000 patient-days), followed by hemato-oncology wards, and infectious disease wards. Occurrence of CDAD was associated with ≥3 stool pus cells per high power field (p=0.018), prior use of metronidazole (p=0.029), high usage of beta-lactamase stable penicillins (p=0.046), and anaerobe-active antibiotics (p=0.029). No attributable mortality was found. The incidence of CDAD was lower than that previously observed (1.0/1000 patient-days in 2003, p<0.001). This study showed a lower incidence of CDAD and absence of attributable mortality. The impact of hand hygiene promotion and other infection control measures on decreasing incidence of CDAD warrants further elucidation.

Comparison of Clostridium Difficile Associated Diarrhea Detection by Enzyme Linked Immunosorbent Assay (EIA) and Polymerase Chain Reaction (PCR) in Autologous Hematopoietic Stem Cell Transplant (AHSCT) Recipients

Abstract 4739 Background:Diarrhea is a frequent complication of autologous hematopoietic stem cell transplantation and is a common cause of morbidity. Clostridium difficile associated diarrhea (CDAD) is the most common cause of nosocomial infections. Detection of CDAD is widely performed using enzyme linked immunosorbent assay (EIA) to C. difficile toxins A and B because of its technical ease of use and rapid results. The sensitivity of EIA is 60%, but the sensitivity increases with repeated testing. Recently, detection of CDAD by Polymerase Chain Reaction (PCR) methodology has resulted in rapid detection of amplified C. difficile toxin (CDT) B chromosomal material and has been shown to be more sensitive than EIA in patients suspected of CDAD; however, no comparison of the two methodologies has been performed in recipients of an autologous hematopoietic AHSCT. Methods:This retrospective analysis of AHSCT recipients at our institution evaluates the incidence of CDAD when using either EIA or PCR. CDAD was assessed at the onset of diarrhea in both cohorts. The time period of interest was from 7 days prior to transplantation to 30 days posttransplanation. In the EIA cohort, three consecutive liquid stools were tested for the presence of CDT A and B by EIA. In the PCR cohort, only one liquid stool was sent for sampling. Our institution adopted PCR methodology on 1 February 2010. Demographic and clinical information were collected to assess CDAD risk. Successful treatment of CDAD was defined as resolution of diarrhea within seven days. Previously published data from our institution have shown the incidence of CDAD to be 15% when using EIA methodology. Nominal data were analyzed by Fisher's Exact Test and continuous data were analyzed by Student's T-Test. Results:A total of 159 patients were screened; and 16 patients were excluded because they did not have a CDAD test performed. Seventy-three were included in the EIA cohort and 69 were included in the PCR cohort. Clinical characteristics were similar between the groups. Known risk factors for CDAD including days in the hospital, days of neutropenia, and days of prophylactic and intravenous antibiotics used were similar between the cohorts. The incidence of a positive CDAD test was higher in the EIA cohort compared to the PCR cohort (18% vs. 7% [p = 0.049]). The duration of diarrhea was longer in the EIA cohort as compared to the PCR cohort (7.3 days vs. 5.5 days [0.016]). Of the three consecutive EIA tests sent, the first was positive only 30% (4/13) of the time. Metronidazole was the first-line agent used in all cases. Response to therapy was poor in both the EIA and PCR cohorts with rates of 30% and 20%, respectively. No fatalities occurred in either group as a result of CDAD. Conclusion:The incidence of diarrhea was significantly shorter in the PCR cohort as compared to the EIA cohort. The duration of diarrhea was significantly shorter in the PCR group as compared to the EIA cohort. It is possible that repeated testing for CDAD by EIA decreases the specificity of the test or that the EIA is detecting a non-toxigenic C. difficile enterotoxin. Because our patient population has additional causes of diarrhea including mucosal irritation caused by chemotherapy, additional studies are needed to discern the discrepancies between both methodologies.EIA Cohort (n=73)PCR Cohort (n=69)P valueAge (median, years)61600.163Race (n,%)36 (49)38 (55)0.521Caucasion19 (26)20 (29)African American17 (23)11 (16)Hispanic1 (1)0 (0)OtherMale (n,%)71 (97)64 (93)0.265Karnofsky Performance Status (median,%)90900.932Disease (n,%)56 (77)45 (65)0.625Myeloma15 (20)21 (30)Lymphoma2 (3)3 (5)OtherCDAD (n,%)13 (18)5 (7)0.049Diarrhea Duration (mean, days)7.35.50.016 (−3.32 to −0.16)CDAD treatment response (n,%)4 (30)1 (20)0.568Days of Neutropenia (mean, days)76.70.553 (−1.01 to 0.54)Days of oral antibiotics (mean, days)4.54.30.774 (−1.04 to 0.77)Days of IV antibiotics (mean, days)7.35.50.170 (−4.33 to 0.77) Disclosures:No relevant conflicts of interest to declare.

Savings from the use of a probiotic formula in the prophylaxis of antibiotic-associated diarrhea

Objective:Antibiotic-associated diarrhea (AAD) and particularly Clostridium difficile-associated diarrhea (CDAD) are the most common causes of healthcare associated infectious diarrhea. A double-blind, dose response, placebo-controlled trial of the probiotic formula (Bio-K+ Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R formula) for prophylaxis of AAD and CDAD was published in 2010. The Bio-K+ Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R formula is a registered trademark of Bio-K Plus International Inc. (Laval, Québec, Canada). Results indicated that the incidence of AAD and CDAD were lower for patients assigned to the probiotic formula compared with the placebo option. The present study aims to estimate the savings in direct medical costs that might result from the use of two different doses of the probiotic formula vs placebo.Methods:A cost-consequence analysis was conducted to compare the two doses of the probiotic formula compared to placebo. The analysis was based upon published data and adjusted to the North American context.Results:Economic analyses showed that the use of the probiotic formula would result in estimated mean per patients savings of US$1968 for the single dose and US$2661 for the double dose compared with the placebo option if used an average of 13 days by all patients at risk of developing AAD and CDAD.Limitations:Several key parameters considered within the economic model were not captured within the Gao et al. study. Numerous sensitivity analyses were conducted to address this issue.Conclusion:The use of the probiotic formula in prophylaxis of AAD and CDAD would lead to estimated savings in direct medical costs that would substantially offset its acquisition cost. Treating 1000 hospitalized patients on antibiotics with the double dose of the product compared to current practice would save a single payer system the sum of $2,661,218.